Complementary and alternative medicine use for supportive care in childhood cancer - Prevalence of use, effectiveness, safety and clinical practice

Childhood cancer treatment protocols have been successful due to the prompt and accurate diagnosis, availability of care, and access to high-quality medical resources. As the survival rates increase in high-income countries (HIC), the emphasis has shifted from survival to survival, emphasizing quality of life. The health complaints and adverse effects of cancer treatment are burdensome for children, yet many of the most burdensome ones lack adequate conventional medical treatment. To help cope with and alleviate these health challenges, parents seek ways to improve their children's quality of life and use supportive care modalities, including complementary and alternative medicine (CAM). The global aim of this doctoral thesis was to delineate the use, effectiveness, safety, and practice of supportive care in childhood cancer. The project was conducted in different stages to achieve the aims, and mixed methods were used. A cross-sectional survey was implemented to assess the prevalence and associations of supportive care use in Norway among children with cancer. Two systematic literature reviews were conducted to evaluate the effect, safety, and types of modalities used to help patients cope with the adverse effects and health complaints of cancer treatment. Semi-structured interviews were used to assess the clinical experiences and perceptions healthcare providers working with pediatric oncology patients have regarding supportive care. Finally, interviews were also used to evaluate how providers perceive and evaluate risk when patients use conventional and supportive care. Over half of the parents who participated in the survey used supportive care, and 47% used CAM to help their children cope with the adverse effects of cancer treatment. Less than 10% reported adverse effects from supportive care modalities. Results from the meta-analysis demonstrated that CAM (including acupuncture and hypnosis) has a significant effect (p<.00001) on the intensity and/or episodes of chemotherapy-induced nausea and vomiting (CINV). Furthermore, over 60% of the included studies lacked reporting the absence or presence of adverse effects. This result makes it difficult to evaluate the safety associated with these modalities. The semi-structured interviews showed that healthcare providers' main aim is to identify the parent's treatment goals and help the children with their most immediate complaints. Among providers, safety was the most important criterion considered when recommending a supportive care modality. This criterion was based on a risk versus benefit evaluation. Providers emphasized the importance of open and respectful communication with parents about supportive care modalities, as these modalities empower parents through the care of their children. Parents in Norway widely use supportive care modalities; therefore, they need information on the effectiveness and safety of these modalities. Healthcare providers such as doctors, nurses, and rehabilitation personnel should have access to reliable information on these modalities to communicate with patients properly. As survival rates increase and late and long-term effects become more prevalent, it is essential to investigate safe and non-invasive treatments to alleviate this burden in children with cancer and survivors. Further methodologically rigorous research should be conducted to investigate the effectiveness and safety of supportive care modalities. In conclusion, if appropriately used by professional healthcare providers, supportive care modalities may decrease health complications from cancer treatment and contribute to a better quality of life for children with cancer and their families.Behandlingsprotokoller for barn med kreft har vært vellykket på grunn av hurtige og tydelige diagnoser, tilgjengelig behandling og tilgang til medisinsk personell med høy faglig kompetanse. Tidligere ble det fokusert bare på overlevelse. Nå blir det lagt mer vekt på livskvalitet fordi overlevelsesraten har økt i høyinntekstland. Helseutfordringer og bivirkninger som følge av kreftbehandling er svært belastende for barn. Likevel får disse barna ikke tilstrekkelig medisinsk behandling for mange av disse plagene. Foreldre søker derfor alternativer som kan hjelpe barna med å håndtere og lindre disse helseutfordringene. Slike alternativer er bruk av støttende behandlingsformer som inkluderer alternativ behandling. Målet med denne doktorgradsavhandlingen var å kartlegge hvordan barn med kreft bruker støttende behandlingsformer, hvor effektiv og trygg disse behandlingene er og hvordan behandlingsformene blir praktisert. Forskningsprosjektet ble utført i flere trinn og det ble benyttet en mixed methods tilnærming. Vi gjennomførte en spørreundersøkelse for å evaluere forekomsten og assosiasjonene knyttet til støttende behandlingsformer av barn med kreft i Norge. Vi gjennomførte to systematiske litteraturgjennomganger for å evaluere effekt, trygghet og hvilke behandlingsformer som ble brukt for å hjelpe pasienter med å håndtere bivirkninger og helseplager knyttet til kreftbehandling. Vi benyttet semistrukturerte intervjuer for å evaluere hvilke kliniske erfaringer og holdninger pediatrisk helsepersonell har med å gi støttende behandling til barn med kreft. Til slutt brukte vi data fra disse intervjuene til å kartlegge hvordan helsepersonell oppfatter og vurderer risiko når pasienter bruker konvensjonell og støttende behandlingsformer som del av sin kreftomsorg. Mer enn halvparten av foreldrene som deltok i spørreundersøkelsen brukte støttende behandlingsformer, og 47% brukte alternativ behandling for å hjelpe barna sine med å håndtere bivirkninger av kreftbehandling. Færre enn 10% rapporterte om bivirkninger ved bruk av disse behandlingsformene. Resultatene fra meta-analysen viste at alternativ behandling (inkludert akupunktur og hypnose) har en signifikant effekt (p<.00001) på intensitet og/eller tilfeller av kvalme og oppkast etter cellegiftbehahandling. Mer enn 60% av de inkluderte studiene i oppsummeringene manglet informasjon om bivirkninger. Dette gjør det vanskelig å evaluere sikkerheten knyttet til disse behandlingsformene. De semistrukturerte intervjuene viste at hovedmålet til behandlerne var å kartlegge foreldrenes mål for behandlingen og hjelpe barna med de verste plagene. Når behandlerne anbefalte pasientene å bruke støttende behandlingsformer, var det viktigste kriteriet at behandlingen skulle være trygt. Dette kriteriet var basert på en risiko -nytte evaluering. I tillegg understreket behandlerne hvor viktig det var å snakke åpent og respektfullt med foreldrene om disse behandlingsformene. En slik samtale er viktig fordi ved bruk av disse behandlingsformene blir foreldrene involvert i kreftomsorgen av sine barn. Dette styrker foreldrene. Foreldre til barn som har kreft, benytter ofte støttende behandlingsformer. Helsepersonell som leger, sykepleiere og rehabiliteringspersonell bør derfor ha tilgang til pålitelig informasjon om disse behandlingsformene for å kunne kommunisere med pasientene på en god og informativ måte. Overlevelsesraten øker, og seneffekter blir mer utbredt blant kreftoverlevere. Derfor er det viktig å undersøke hvilke behandlinger some er trygge og mindre belastende for barnekreft-overlevere. Det er nødvendig å gjennomføre mer (grundig) forskning for å kartlegge hvor effektive og trygge disse behandlingsformene er. Konklusjon: Støttende behandlingsformer kan redusere helseplager etter kreftbehandling hos barn hvis de brukes på en riktig måte, utført av kompetente behandlere. Dette kan bidra til bedre livskvalitet for barn med kreft og familiene deres

Use of Complementary and Alternative Medicine in the context of cancer; prevalence, reasons for use, disclosure, information received, risks and benefits reported by people with cancer in Norway

Background Research exploring the use of specific Complementary and Alternative Medicine (CAM) modalities by Norwegian cancer patients is sparse. The aims of this study were therefor to map the different CAM modalities cancer patients use and further investigate their rationale for use, communication about use, self-reported benefits and harms, and their sources of information about the different modalities. Methods In cooperation with the Norwegian Cancer Society (NCS), we conducted an online cross-sectional study among members of their user panel with present or previously cancer (n = 706). The study was carried out in September/October 2021 using a modified cancer-specific version of the International Questionnaire to Measure Use of Complementary and Alternative Medicine (I-CAM-Q). In total, 468 members, 315 women and 153 men, agreed to participate resulting in a response rate of 67.2%. The study was reported in accordance with the National Research Center in Complementary and Alternative Medicine’s (NAFKAM) model of reporting CAM use. Results A large proportion of the participants (79%, n = 346) had used some form of CAM with a mean of 3.8 modalities each (range 1-17); 33% (n = 143) had seen a CAM provider, 52% (n = 230) had used natural remedies, while 58% (n = 253) had used self-help practices. Most of the participants used CAM to increase their quality of life, cope with the cancer disease or for relaxation/well-being (64%-94%), mostly with high satisfaction and low rates of adverse effects. Few used CAM to treat cancer or prevent it from spreading (16%, n = 55). The main information sources were health care providers (47%), the internet (47%), and family and friends (39%). More than half (59%) of the cancer patients discussed their use of at least one CAM modality with a physician. Conclusions The results of this survey will provide health professionals with more in-depth insight into the patterns of CAM use by cancer patients and facilitate better-informed discussions with their patients. Considering the high use of CAM, reliable information provision supporting cancer care providers’ knowledge and health literacy among patients as well as good communication are crucial. The cooperation between the NCS and NAFKAM provides an example of how to address these issues

Alternativ behandling som støttebehandling til kovensjonell behandling hos barn og uge med kreft

At barnet ditt får en kreftdiagnose er en rystende beskjed som snur livet opp ned for mange familier. Behandlingen er krevende og mange barn og unge får plager de må leve med lenge. Foreldrene ønsker naturlig nok å gjøre det de kan for å lindre disse plagene. Mange velger derfor alternativ behandling som støttebehandling til konvensjonell behandling og for å bedre barnas livskvalitet

Prevalence of late and long-term effects of cancer (treatment) and use of complementary and alternative medicine in Norway

Background The increasing number of patients surviving cancer leads to more people experiencing late and long term-effects from the disease and its treatment. Fatigue, sleep disorders, early menopause, pain, and nerve damage are commonly reported. Methods helping people to recover after cancer treatment are therefore essential. The aims of this study were threefold; (1) to determine the level of cancer patients suffering from late and long-term effects of cancer diagnosis and treatment in Norway, (2) explore complementary and alternative medicine (CAM) modalities used for managing these adversities, and (3) describe self-perceived benefits and harms of the CAM interventions. Methods The study was conducted in cooperation with the Norwegian Cancer Society (NCS) and consisted of an online cross-sectional study among members of the NCS user panel with present or previous cancer (n = 706). The study was carried out in September/October 2021 using a modified cancer-specific version of the International Questionnaire to Measure Use of Complementary and Alternative Medicine (I-CAM-Q). A total of 315 women and 153 men agreed to participate, resulting in a response rate of 67%. Results Most of the participants (83%) suffered from late and long-term effects of cancer treatment; mostly fatigue (59.2%), sleep disorder (41.5%), hot flashes (39.2%), nerve damage (polyneuropathy, 38.0%), and pain (36.6%) with a mean number of 5.1 different late and long-term effects. Late and long-term effects were positively associated with younger age and college/university education. Nearly half of the participants experiencing late and long-term effects (43%) reported having used CAM to treat these complaints. Most frequently used were self-help practices (26%) such as relaxation therapy (19%), yoga (14%) and meditation (13%), but also visits to CAM providers were reported by 22%. Herbal- and other natural remedies to treat late and long-term effects were used by 13%. A high percentage of CAM users reported self-perceived improvements of their symptoms (86% for self-help practices, 90% for visits to CAM providers). Few experienced adverse effects of the CAM treatment. Conclusion A large proportion of cancer patients suffered from a wide range of late and long-term effects of cancer diagnosis and treatment, and they use CAM to treat these complaints to a rather high degree. Relaxation therapy, yoga, meditation, massage, and acupuncture were the most frequently used therapies regardless of complaint. The therapies used are generally considered to be both safe and beneficial for the respective complaint, indicating that the participants seem to be well informed about the choices they make

Progress in the Fremantle Primary Prevention Study- A Pilot Study of Risk Factor Modification for Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in 40-80year olds in Australia. Many of the risk factors though modifiable are often undiagnosed and hence untreated. Increasingly, general practice is recognised as being well positioned but under-utilised in attempts to improve primary prevention. The study aims to monitor the changes in CVD risk following delivery of high and low intervention strategies at the GP level. Methods: 1200 participants in total were recruited during routine surgery attendances from 3 WA general practices since November 2006. Baseline data was collected on all. One group then received standard care as per best practice guidelines with 3 monthly follow-up to 12 months. The second group received standard care as per best practice guidelines delivered by their GP with no scheduled interim follow-up but with follow-up at 12 months after study commencement. Data on risk factor indicators was measured at each contact and a composite score on global cardiovascular risk calculated using the New Zealand Risk Calculator. Principal Findings: In January 2008, data was recorded on 1178 participants at baseline (22 withdrew), 3 month data on 537, 6 month data on 458 and 9 month on 272 and 12 month data on 96. Interim data will be presented. While a significant proportion of the community are already known to have cardiovacular risk factors, GPs and their practice staff are ideally positioned to assess the extent of this potential morbibity and institute treatment modalities and programs to reverse and modify them

Organ-specific COP1 control of BES1 stability adjusts plant growth patterns under shade or warmth

Under adverse conditions such as shade or elevated temperatures, cotyledon expansion is reduced and hypocotyl growth is promoted to optimize plant architecture. The mechanisms underlying the repression of cotyledon cell expansion remain unknown. Here, we report that the nuclear abundance of the BES1 transcription factor decreased in the cotyledons and increased in the hypocotyl in Arabidopsis thaliana under shade or warmth. Brassinosteroid levels did not follow the same trend. PIF4 and COP1 increased their nuclear abundance in both organs under shade or warmth. PIF4 directly bound the BES1 promoter to enhance its activity but indirectly reduced BES1 expression. COP1 physically interacted with the BES1 protein, promoting its proteasome degradation in the cotyledons. COP1 had the opposite effect in the hypocotyl, demonstrating organ-specific regulatory networks. Our work indicates that shade or warmth reduces BES1 activity by transcriptional and post-translational regulation to inhibit cotyledon cell expansion.Peer reviewe

Characterization of MgtC, a Virulence Factor of Salmonella enterica Serovar Typhi

The MgtC is a virulence factor in Salmonella Typhimurium that is required for growth at low-Mg2+ concentrations and intramacrophage survival. This gene is codified in a conserved region of the Salmonella pathogenicity island 3 (SPI-3), and is also present in the chromosome of other Salmonella serovars. In this study we characterized the MgtC factor in S. Typhi, a human specific pathogen, by using mgtC and SPI-3 mutant strains. We found that MgtC is the most important factor codified in the SPI-3 of S. Typhi for growth in low-Mg2+ media and survival within human cells. In addition, by using reporter genes we determined that the low-Mg2+ concentration, acidic media and PhoP regulator induce mgtC expression in S. Typhi. We suggest that MgtC is the most important virulence factor codified in the SPI-3 of S. Typhi

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes